The rhinal cortices (perirhinal areas 35-36 and entorhinal cortex, EC) play a critical role in high-order perceptual/mnemonic functions and constitute the main route for impulse traffic in and out of the hippocampus. However, there is a discrepancy between anatomical and physiological data about this network. Indeed, tracing studies indicate that the perirhinal cortex forms strong reciprocal connections with the neocortex and EC. In contrast, physiological findings indicate that perirhinal transmission of neocortical and entorhinal inputs occur with an extremely low probability. The general objectives of this proposal are: (A) to shed light on the inhibitory mechanisms that limit impulse traffic through the rhinal cortices and (B) to identify the afferents that allow the rhinal cortices to overcome this inhibition, focusing on inputs from the medial prefrontal cortex (mPFC) and amygdala. To these ends, we will: (1) identify the transmitter and synaptic targets of neocortical and entorhinal axons to areas 35, 36 and EC using anterograde (or retrograde) tracer injections in the temporal neocortex or particular rhinal fields coupled to immunocytochemistry at the electron microscopic level. (2) determine the effect of neocortical and entorhinal stimuli on rhinal neurons recorded in vitro with the whole cell patch method and in vivo with sharp micropipettes. (3-4) determine how the mPFC and amygdala affect impulse traffic across the rhinal cortices. This will be studied using a combination of anatomical and physiological experiments. Anatomical experiments will require anterograde tracer injections restricted to particular regions of the mPFC and amygdala, and the same methods as in (1). Physiological experiments will involve inverse dialysis of picrotoxin in mPFC or amygdala and multiple simultaneous extra- and intracellular neuronal recordings of rhinal neurons in vivo. Since the rhinal cortices are primarily damaged during early stages of Alzheimer's disease, this basic research program may improve our understanding of memory disorders.